Molecular imaging has entered a new era in which different imaging modalities have become available for in vivo studies of disease-defining targets. These imaging modalities include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and optical imaging, which complement each other in many ways. For example, PET provides high sensitivity but relatively low resolution while MRI provides high resolution but low sensitivity. PET provides high quantitative capacity compared to SPECT but production of PET radiotracers is limited, as it requires a cyclotron to produce positron-emitting carbon-11 and fluorine-18. Production of SPECT radiotracers is more affordable as it uses generators that are more readily available. PET, SPECT, and MRI are the primary imaging modalities in clinical settings.
One of the key targets for molecular imaging is myelin membranes. In the vertebrate nervous systems, myelination is one of the most fundamental biological processes that provide a unique structure that fosters rapid and efficient conduction of impulses along axons. Destruction or changes in myelination have been considered as a causative event in numerous neurological diseases such as multiple sclerosis (MS). Significant efforts have been made to delineate molecular mechanism of demyelination/remyelination and develop novel therapeutics aimed at myelin repair. However, there is still a need to directly detect and quantify myelin changes in vivo in both preclinical and clinical settings.
Magnetic resonance imaging (MRI) is widely used in brain imaging in MS and other myelin-related diseases. However, MRI is not a specific measure of myelination, as MR signals reflects only a change in tissue water content, which is a non-specific measure of the overall changes in macroscopic tissue injury.
Near-infrared (NIR) fluorescence imaging is a powerful tool for in vivo preclinical studies of disease progression in animal models. Use of NIR imaging depends on the availability of target-specific molecular probes, for example, those that can be delivered through membranes or the intact blood-brain barrier. In general, light absorption decreases with increasing wavelength. Below 650 nm, tissue absorption leads to small penetration in a depth of only a few millimeters. The absorption coefficient of tissue is considerably smaller in the near infrared region (650 nm-900 nm) and light can penetrate more deeply into the tissues to depths of several centimeters.
Recently, near-infrared fluorescence imaging, have been explored for in vivo detection of amyloid-βdeposits using a near-infrared dye developed by Gremlich et al. (Gremlich, H. U. et al. In vivo detection of amyloid-βdeposit by near-infrared imaging using an oxazine-derivative probe. Nat. Biotechnology. 23, 577-583 (2005)). In order to make the detection and quantification of myelin more practical and less burdensome, novel near-infrared imaging probes are needed to take advantage of the optical imaging modality, such as bioluminescence imaging and fluorescent molecular tomography that have recently been developed.